1. Field of the Invention
The invention relates to a method and a device for examining urine for particulate constituents, in particular cells or crystalline substances. The examination of urine is of great importance for medical diagnostics, including medical check-ups.
2. Prior Art
In recent years the cytology of urine has gained increasing importance in the search for tumors in the urinary tract. This is certainly also due to the fact that preventive medicine provides for an increasing number of check-ups of persons who are susceptible to tumor formation, e.g., workers in the dye and rubber industries. Routine cytological methods are used not only for clarifying dysurias and hematurias of unknown origin but also for monitoring the development of carcinomas of the urinary bladder subjected to transurethral treatment. The same applies to radiotherapy, which is monitored by cytodiagnostics methods in the case of both urological and gynecological indications.
The cytology of urine is based on the investigation of exfoliating cells which have separated from the tissue and flaked off into the urine, and which are discharged in the urine. The cellular constituents of urine may originate from neoplasias of the kidneys and of the urinary tracts or from the walls of the urinary bladder, and may also result from inflammatory processes in the whole urogenital system. Further, it is possible that squamous epithelia from the genital tract are discharged in the urine of women, while cell material from the prostate gland may be discharged in the urine of men. Today, the urine samples for cytodiagnosis are taken by a specialist (urologist), or by a general practitioner if this is indicated, and submitted to a cytologist. They may be obtained by one of the following methods:
Spontaneous urine, normally morning urine, is collected by the patient who then brings it to the doctor; PA1 Urine samples are withdrawn by means of catheters, for example if contamination of the sample with cells from the genital tract is to be avoided; PA1 In special cases, cell material may be obtained from ureters and renal pelvis by catheterization or collected by cystoscopy. PA1 Production of a cell sediment by centrifugation. This means that urine samples between 2 and 10 ml in total volume are centrifuged, the supernatant is sucked off, and the sediment is processed into cell smears. If the concentration of cellular material in the urine is low, larger amounts of the urine sample submitted have to be distributed to several centrifuge tubes and processed separately, the individual sediments then being combined in one smear. PA1 Some cytological laboratories usually process the urine samples by the cytocentrifuge. After shaking, 0.2 ml is drawn off and centrifuged; in this case a microscopic slide that is placed into the centrifuge is directly smeared with the cells. PA1 When using the so-called filter technique, 10 mm of urine is poured into a filter head which is provided, for example, with millipore filters (pore size 5 .mu.m). The liquid is sucked through the filter, and the cells are retained on the filter surface. The cells are then transferred from the filter to the microscopic slide, fixed and stained. PA1 May-Gruenwald-Giemsa stain PA1 Papanicolaou's stain PA1 Methylene blue stain according to Loffler
The urine samples of different volume are sent to the cytological laboratory, either in native form or with a fixing agent, e.g., methanol acetic acid, having been added.
The cells are extracted from the urine sample by different methods, which depend in particular on the experience of the diagnostic laboratory concerned. The methods normally used at present are described below:
Which dyes are used for the urine sediment smears depends on the requirements of the method of visual diagnosis to be applied. The following staining method are normally used:
All known methods have the drawback that the cells remain in the urine for a relatively long time, which renders diagnosis difficult because the cells undergo autolytic changes after a relatively short time. To ensure a reliable and correct diagnosis, it is therefore very important that the state of the cells immediately after collection be maintained. In practice, however, gynecological cytology tends to become a "mailing" process because for various reasons a large percentage of the samples to be examined has to be mailed to the laboratory. This means that during the time between collection and preparative treatment-i.e., 1 or 2 days or even longer-the urine samples are exposed to various influences which may render diagnosis difficult or render the result incorrect. Only in exceptional cases and under the most favorable conditions can the requirement be satisfied that a urine sample should be processed not later than two hours after collection, which is generally accepted by experts in the field.
Since a correct diagnosis result can only be achieved if the cells are well preserved, incorrect judgments in the evaluation or urine sediments are unavoidable with the conventional methods mentioned above. Depending on the properties and the composition of the urine, e.g., its pH value, cytolysis-which starts already in the urinary bladder-proceeds until the cell samples are fixed. However, satisfactory cell fixation is only achieved in an alcoholic medium of at least 70 percent; this is why in practice the alcohol cannot be added before cell collection, i.e., before separation of the urine.